The production of beta-lactamase (penicillinase) enzymes by bacteria is still an important factor in bacterial resistance to penicillin therapy. An understanding of the mechanism of action of these enzymes is thus fundamental to the design of improved beta-lactam antibiotics. The object of the proposed research is to explore further the active site chemical functionality and conformational adaptability of a series of beta-lactamases througth a detailed study of the elemental events of beta-lactamase catalysis using a number of fluorescent substrates and through an investigation of the mechanism of interaction of these enzymes with a number of novel substrates/inhibitors. These studies should lead to a more detailed functional picture of the beta-lactamase active site, to new classes of effective beta-lactamase inhibitors and possibly to new directions for antibiotic development.